BME Distinguished Speaker: James Dahlman, PhD,; Emory University

"Testing thousands of nanoparticles in vivo"

Abstract: RNA can change the expression of any gene. However, whether the drug is comprised of siRNA, mRNA, or another nucleic acid, it is limited by one problem: drug delivery. Chemists can design thousands of distinct nanoparticles to deliver RNA to the desired cell type. Yet after nanoparticles are synthesized, their ability to deliver drugs is often evaluated using in vitro systems devoid of a liver, kidney, spleen, immune system, blood flow, and other selection pressures known to affect nanoparticle delivery in vivo. Here we describe DNA barcoding platforms to quantify how hundreds of chemically distinct nanoparticles deliver mRNA or siRNA with cell type (i.e., not just tissue) resolution in a single experiment. Using this high throughput, iterative, in vivo approach, we have identified manufacturable nanoparticles with tropism to non-liver cell types in mice and nonhuman primates (NHPs). This includes well-tolerated LNPs that deliver mRNA to hematopoietic stem cells in NHPs at low doses after an intravenous administration.